Abstract Rural populations in the US experience disparities in cancer screening, cancer treatment, and survival for cancer patients compared to urban populations. Cancer survivors may experience late effects caused by the cancer treatment such as cardiotoxicity and subsequent cardiovascular disease (CVD). The higher rates of obesity and smoking, lower health insurance coverage rates, and decreased access to primary care in rural populations may contribute to higher incidence rates of chronic diseases among rural cancer survivors. Higher rates of opioid use among cancer survivors and among rural populations are a concern, but few studies are available on rural cancer survivors. The Population-Based Rural Cancer Survivors Cohort will include rural prostate, breast and colorectal cancer patients diagnosed from 1997 to 2015. The cohort will be developed with the Utah SEER Cancer Registry, which has data linked to the Utah Population Database (UPDB), and includes electronic medical records, statewide healthcare facility data, residential histories, family history records, and the All-Payer Claims Database (APCD). We will also develop cohorts for the same cancers in the SEER-Medicare data focusing on the elderly population including all SEER registries in the data other than Utah. The specific aims of our study are: 1) to assess the risk of diabetes, CVD and depression among rural breast, prostate and colorectal cancer patients in comparison to their respective urban cancer patient groups in a population-based cohort. We will further investigate whether cancer treatments contribute to adverse outcomes among rural cancer survivors. 2) to evaluate the risk of opioid use disorders among rural breast, prostate and colorectal cancer patients in comparison to urban cancer patients and the association of opioid use disorders with survival, 3) to estimate the comorbidity trajectory over time after cancer diagnosis, as well as risks of diseases in the major body systems among rural breast, prostate and colorectal cancer patients in comparison to their respective urban cancer patient groups. Aim 3 will allow for capture of potential new outcomes that may be more important among rural cancer survivors. Our study is innovative in assessing the risk of long-term disease incidence among rural cancer survivors for the first time, with a longitudinal approach, in a large-scale population-based cohort in Utah and in the elderly in the US. Our Population-Based Rural Cancer Survivors Cohort will contribute significantly to rural cancer survivorship by identifying specific outcomes that are more common among rural cancer survivors for prevention of disease and improved survival. We will also identify potential modifiable factors that can be targeted for rural cancer survivors with interventions such as access to care with telemedicine and tobacco cessation. Future directions include the development of risk prediction modeling specifically for rural cancer survivors, that would help to identify rural cancer survivors at high risk who would benefit from specific preventive interventions.